Predictive Risk Factors and Scoring Systems Associated with the Development of Hepatocellular Carcinoma in Chronic Hepatitis B

Simple Summary Chronic hepatis B still remains a global epidemic and one of the leading causes of hepatocellular carcinoma worldwide. We aimed to find out possible factors that could predict hepatocellular carcinoma development, as well as to compare the predictive performance of various, well-known, risk models in 632 patients with chronic hepatitis B. In our cohort, 34 patients developed hepatocellular carcinoma during follow-up. We found that patients that had cirrhosis, were males, had increased alcohol consumption and were older, had increased risk for cancer development in the multivariate analysis. Of the various risk models that were tested, Core promoter mutations and cirrhosis-HCC (GAG-HCC) and Platelet Age Gender-HBV (PAGE-B) risk models had the greatest performance; however, this performance significantly declined in the subgroup of patients with cirrhosis. In conclusion, certain baseline factors and risk models seem to predict the development of hepatocellular carcinoma in patients with chronic hepatitis B; however, this prediction declines in the subgroup of patients with cirrhosis and thus, we need novel risk models to be developed specifically for these patients.Abstract Chronic hepatitis B (CHB) infection constitutes a leading cause of hepatocellular carcinoma (HCC) development. The identification of HCC risk factors and the development of prognostic risk scores are essential for early diagnosis and prognosis. The aim of this observational, retrospective study was to evaluate baseline risk factors associated with HCC in CHB. Six hundred thirty-two consecutive adults with CHB (n = 632) [median age: 46 (IQR: 24)], attending the outpatients' Hepatology clinics between 01/1993-09/2020 were evaluated. Core promoter mutations and cirrhosis-HCC (GAG-HCC), Chinese University-HCC (CU-HCC), risk estimation for hepatocellular carcinoma in chronic hepatitis B (REACH-B), Fibrosis-4 (FIB-4), and Platelet Age Gender-HBV (PAGE-B) prognostic scores were calculated, and receiver operating curves were used to assess their prognostic performance. HCC was developed in 34 (5.38%) patients. In the multivariable Cox regression analysis, advanced age (HR: 1.086, 95% CI: 1.037-1.137), male sex (HR: 7.696, 95% CI: 1.971-30.046), alcohol abuse (HR: 2.903, 95% CI: 1.222-6.987) and cirrhosis (HR: 21.239, 95% CI: 6.001-75.167) at baseline were independently associated with the development of HCC. GAG-HCC and PAGE-B showed the highest performance with c-statistics of 0.895 (95% CI: 0.829-0.961) and 0.857 (95% CI: 0.791-0.924), respectively. In the subgroup of patients with cirrhosis, the performance of all scores declined. When treated and untreated patients were studied separately, the discriminatory ability of the scores differed. In conclusion, HCC development was independently associated with advanced age, male sex, alcohol abuse, and baseline cirrhosis among a diverse population with CHB. GAG-HCC and PAGE-B showed high discriminatory performance to assess the risk of HCC development in these patients, but these performances declined in the subgroup of patients with cirrhosis. Further research to develop scores more specific to certain CHB subgroups is needed.